Metabolomics is the systematic analysis of low-molecular weight compounds (metabolites) within biological systems that represent molecular endpoints of gene expression and environmental exposures. A major goal of metabolomics is achieving better understanding of the pathophysiology of complex disease processes while elucidating mechanisms of action of nutrients, toxins, and/or drugs. Multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) is a high-throughput microseparation platform that is ideal for the analysis of polar/ionic metabolites from volume-restricted biological samples. This thesis includes two major metabolomics projects using MSI-CE-MS that are aimed at contributing new advances in public health and chronic disease prevention. Chapter II presents an analysis of the metabolome from patients with phenylketonuria (PKU) — a genetic disease affecting phenylalanine (Phe) metabolism that requires lifelong dietary restriction to prevent irreversible intellectual disabilities. A targeted and nontargeted metabolomics approach using matching urine and plasma samples was conducted to confirm known markers of PKU and identify new markers associated with dietary adherence and disease progression. Along with increased excretion of Phe catabolites in urine, high plasma Phe was associated with decreased excretion of acylcarnitines and greater excretion of histidine catabolites, suggesting impaired fatty acid oxidation and micronutrient deficiencies, respectively. Overall, this may provide a strategy to objectively monitor dietary adherence beyond standard dietary records or patient recall. Chapter III investigates the impact of electronic cigarette smoke exposure on the placental metabolome as a model cell line of fetal development. Evidence of altered amino acid metabolism, in addition to changes in acylcarnitines and metabolites associated with cellular proliferation, were observed in more susceptible first trimester placental cells and were attributed to flavouring agents irrespective of nicotine dosage. This work supports the hypothesis that flavoured e-cigarette formulations pose a significant health risk in comparison to unflavoured formulations and supports the need for further risk assessment and careful regulation of these products to prevent deleterious birth outcomes in pregnant mothers. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23072 |
| Date | January 2017 |
| Creators | Wild, Jennifer |
| Contributors | Britz-McKibbin, Philip, Chemical Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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